INHIBITORY EFFECT OF HEPARIN ON SEROTONIN-INDUCED HYPERPLASIA AND HYPERTROPHY OF SMOOTH-MUSCLE CELLS

Serotonin (5-HT) produces both hyperplastic and hypertrophic effects o n smooth muscle cell (SMC) in culture. Heparin is known to inhibit ser um-induced hyperplasia of SMC but has not been previously tested on th e stimulatory effect of 5-HT on SMC. Our present data show that at 24 h heparin inhibited by 50% the stimulation of H-3-thymidine incorporat ion into bovine pulmonary artery SMC and at 7 days totally reversed bo th cellular proliferation and enlargement of SMC produced by 1 mu M 5- HT. Heparin failed to alp ter 5-HT uptake by SMC, but inhibited the st imulation of tyrosine phosphorylation of GTPase-activating protein, a proposed intermediate in the 5-HT stimulatory process. Thus heparin in hibits both hyperplastic and hypertrophic effects of 5-HT on SMC, perh aps through the inhibition of a phosphorylated intermediate protein.